Fumarate reductase (Frd) is an integral membrane protein that catalyzes the final step of anaerobic respiration when fumarate is the terminal electron acceptor. In this reaction the reduction of fumarate to succinate is coupled to the oxidation of reduced dihydroquinone. Frd exhibits high sequence and catalytic similarity to succinate ubiquinone oxidoreductase (SQR or Complex II) of the aerobic respiratory chain. Both proteins are complexes of four polypeptides: a flavoprotein (mw ~66 kDa), an iron-sulfur protein (mw ~27 kDa), and two transmembrane quinone binding proteins (mws= ~13-15 kDa) for a total molecular weight of 121 kDa. Contained within Frd and SQR are multiple redox centers, including [4Fe-4S], and [3Fe-4S], and [2Fe-2S] iron sulfur clusters and one b-type heme and quinone binding sites. No high resolution structure of a Complex II from any sources has been solved to date. Crystals of Frd have been obtained by us that diffract to 2.8 E resolution at SSRL (compared to 3.5 E resolution on our laboratory generator). The aim of this proposal is to collect the high resolution data from native and derivative crystals necessary to solve the structure of Frd.